Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

Nature Genetics

Volumn 49, Issue 4, 2017, Pages 537-549

  Reynolds, John J ^a   Bicknell, Louise S ^b,ae   Carroll, Paula ^b   Higgs, Martin R ^a   Shaheen, Ranad ^c   Murray, Jennie E ^b   Papadopoulos, Dimitrios K ^d   Leitch, Andrea ^b   Murina, Olga ^b   Tarnauskaite, Zygimante ^b   Wessel, Sarah R ^e   Zlatanou, Anastasia ^a   Vernet, Audrey ^a   Von Kriegsheim, Alex ^b   Mottram, Rachel M A ^a   Logan, Clare V ^b   Bye, Hannah ^f   Li, Yun ^g   Brean, Alexander ^a   Maddirevula, Sateesh ^c   Challis, Rachel C ^b   Skouloudaki, Kassiani ^d   Almoisheer, Agaadir ^c   Alsaif, Hessa S ^c   Amar, Ariella ^f   Prescott, Natalie J ^f   Bober, Michael B ^h   Duker, Angela ^h   Faqeih, Eissa ⁱ   Seidahmed, Mohammed Zain ^j   Al Tala, Saeed ^k   Alswaid, Abdulrahman ^l   Ahmed, Saleem ^m,n   Al Aama, Jumana Yousuf ^m,n   Altmüller, Janine ^o   Al Balwi, Mohammed ^l   Brady, Angela F ^p   Chessa, Luciana ^q   Cox, Helen ^r   Fischetto, Rita ^s   Heller, Raoul ^t   Henderson, Bertram D ^u   Hobson, Emma ^v   Nürnberg, Peter ^o   Percin, E Ferda ^w   Peron, Angela ^x,y   Spaccini, Luigina ^x   Quigley, Alan J ^z   Thakur, Seema ^aa   Wise, Carol A ^ab   Yoon, Grace ^ac   Alnemer, Maha ^c   Tomancak, Pavel ^d   Yigit, Gökhan ^g   Taylor, A Malcolm R ^a   Reijns, Martin A M ^b   Simpson, Michael A ^f   Cortez, David ^e   Alkuraya, Fowzan S ^c   Mathew, Christopher G ^f,ad   Jackson, Andrew P ^b   Stewart, Grant S ^a   more..

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c KING FAISAL SPECIALIST HOSPITAL AND RESEARCH CENTER   (Saudi Arabia)

^d MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

^e VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f GUY S HOSPITAL   (United Kingdom)

^g UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^h NEMOURS ALFRED I DUPONT HOSPITAL FOR CHILDREN   (United States)

ⁱ KING FAHAD MEDICAL CITY   (Saudi Arabia)

^j SECURITY FORCES HOSPITAL   (Saudi Arabia)

^k SR PD Genetic Unit ^*  (Saudi Arabia)

^l KING SAUD BIN ABDULAZIZ UNIVERSITY FOR HEALTH SCIENCES   (Saudi Arabia)

^m KING ABDUL AZIZ UNIVERSITY HOSPITAL   (Saudi Arabia)

ⁿ Princess Al Jawhara Al Brahim Centre of Excellence in Research of Hereditary Disorders   (Saudi Arabia)

^o UNIVERSITY OF COLOGNE   (Germany)

^p EALING HOSPITAL NHS TRUST   (United Kingdom)

^q SAPIENZA UNIVERSITY OF ROME   (Italy)

^r BIRMINGHAM WOMEN S HOSPITAL   (United Kingdom)

^s Pediatric Hospital Giovanni XXIII   (Italy)

^t UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^u UNIVERSITY OF THE FREE STATE   (South Africa)

^v CHAPEL ALLERTON HOSPITAL   (United Kingdom)

^w GAZI UNIVERSITY   (Turkey)

^x UNIVERSITY OF MILAN   (Italy)

^y SAN PAOLO HOSPITAL   (Italy)

^z ROYAL HOSPITAL FOR SICK CHILDREN   (United Kingdom)

^aa Fortis Lafemme ^*  (India)

^ab TEXAS SCOTTISH RITE HOSPITAL FOR CHILDREN   (United States)

^ac HOSPITAL FOR SICK CHILDREN   (Canada)

^ad UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^ae UNIVERSITY OF OTAGO   (New Zealand)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; ATR PROTEIN; DNA BINDING PROTEIN;

ALLELE; ARTICLE; CELL ACTIVATION; CELL CYCLE CHECKPOINT; CELL DIVISION; CHROMOSOMAL INSTABILITY; CHROMOSOME BREAKAGE; CLINICAL ARTICLE; CONTROLLED STUDY; DNA DAMAGE; DNA REPLICATION; DONSON GENE; DWARFISM; FEMALE; FRAMESHIFT MUTATION; GENE; GENE DISRUPTION; GENE IDENTIFICATION; GENE LOSS; GENE MUTATION; GENETIC STABILITY; HUMAN; HUMAN CELL; MICROCEPHALIC DWARFISM; MICROCEPHALY; NONSENSE MUTATION; PHENOTYPE; PRIORITY JOURNAL; REPLISOME; CELL LINE; GENETICS; GENOMIC INSTABILITY; MALE; MUTATION;

CELL LINE; DNA DAMAGE; DNA REPLICATION; DNA-BINDING PROTEINS; DWARFISM; FEMALE; GENOMIC INSTABILITY; HUMANS; MALE; MICROCEPHALY; MUTATION;

EID: 85012247268     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3790     Document Type: Article

References (59)

1. Klingseisen, A. & Jackson, A.P. Mechanisms and pathways of growth failure in primordial dwarfism. Genes Dev. 25, 2011-2024 (2011).
2. ODriscoll, M., Ruiz-Perez, V.L., Woods, C.G., Jeggo, P.A. & Goodship, J.A. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat. Genet. 33, 497-501 (2003).
3. Ogi, T. et al. Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel syndrome. PLoS Genet. 8, e1002945 (2012).
4. German, J. Blooms syndrome. I. Genetical and clinical observations in the first twenty-seven patients. Am. J. Hum. Genet. 21, 196-227 (1969).
5. Harley, M.E. et al. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat. Genet. 48, 36-43 (2016).
6. Qvist, P. et al. CtIP mutations cause Seckel and Jawad syndromes. PLoS Genet. 7, e1002310 (2011).
7. Rosin, N. et al. Mutations in XRCC4 cause primary microcephaly, short stature and increased genomic instability. Hum. Mol. Genet. 24, 3708-3717 (2015).
8. Bicknell, L.S. et al. Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nat. Genet. 43, 356-359 (2011).
9. Bicknell, L.S. et al. Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nat. Genet. 43, 350-355 (2011).
10. Guernsey, D.L. et al. Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome. Nat. Genet. 43, 360-364 (2011).
11. Fenwick, A.L. et al. Mutations in CDC45, encoding an essential component of the pre-initiation complex, cause Meier-Gorlin syndrome and craniosynostosis. Am. J. Hum. Genet. 99, 125-138 (2016).
12. Murray, J.E. et al. Extreme growth failure is a common presentation of ligase IV deficiency. Hum. Mutat. 35, 76-85 (2014).
13. Murray, J.E. et al. Mutations in the NHEJ component XRCC4 cause primordial dwarfism. Am. J. Hum. Genet. 96, 412-424 (2015).
14. Shaheen, R. et al. Genomic analysis of primordial dwarfism reveals novel disease genes. Genome Res. 24, 291-299 (2014).
15. Zeman, M.K. & Cimprich, K.A. Causes and consequences of replication stress. Nat. Cell Biol. 16, 2-9 (2014).
16. Zou, L. & Elledge, S.J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300, 1542-1548 (2003).
17. MacDougall, C.A., Byun, T.S., Van, C., Yee, M.C. & Cimprich, K.A. The structural determinants of checkpoint activation. Genes Dev. 21, 898-903 (2007).
18. Nam, E.A. & Cortez, D. ATR signaling: more than meeting at the fork. Biochem. J. 436, 527-536 (2011).
19. Chou, D.M. & Elledge, S.J. Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function. Proc. Natl. Acad. Sci. USA 103, 18143-18147 (2006).
20. Kemp, M.G. et al. Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress. J. Biol. Chem. 285, 16562-16571 (2010).
21. Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285-291 (2016).
22. Milner, R.D., Khallouf, K.A., Gibson, R., Hajianpour, A. & Mathew, C.G. A new autosomal recessive anomaly mimicking Fanconis anemia phenotype. Arch. Dis. Child. 68, 101-103 (1993).
23. Germanaud, D. et al. Simplified gyral pattern in severe developmental microcephalies? New insights from allometric modeling for spatial and spectral analysis of gyrification. Neuroimage 102, 317-331 (2014).
24. Martin, C.A. et al. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat. Genet. 46, 1283-1292 (2014).
25. Trimborn, M. et al. Mutations in microcephalin cause aberrant regulation of chromosome condensation. Am. J. Hum. Genet. 75, 261-266 (2004).
26. Griffith, E. et al. Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. Nat. Genet. 40, 232-236 (2008).
27. Yeo, G. & Burge, C.B. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J. Comput. Biol. 11, 377-394 (2004).
28. Bandura, J.L. et al. humpty dumpty is required for developmental DNA amplification and cell proliferation in Drosophila. Curr. Biol. 15, 755-759 (2005).
29. Cortez, D. Preventing replication fork collapse to maintain genome integrity. DNA Repair (Amst.) 32, 149-157 (2015).
30. Errico, A. & Costanzo, V. Mechanisms of replication fork protection: a safeguard for genome stability. Crit. Rev. Biochem. Mol. Biol. 47, 222-235 (2012).
31. Fuchs, F. et al. Clustering phenotype populations by genome-wide RNAi and multiparametric imaging. Mol. Syst. Biol. 6, 370 (2010).
32. Papadopoulos, D.K. et al. Probing the kinetic landscape of Hox transcription factor-DNA binding in live cells by massively parallel fluorescence correlation spectroscopy. Mech. Dev. 138, 218-225 (2015).
33. Bacia, K. & Schwille, P. Practical guidelines for dual-color fluorescence cross-correlation spectroscopy. Nat. Protoc. 2, 2842-2856 (2007).
34. Sirbu, B.M. et al. Analysis of protein dynamics at active, stalled and collapsed replication forks. Genes Dev. 25, 1320-1327 (2011).
35. Liu, S. et al. ATR autophosphorylation as a molecular switch for checkpoint activation. Mol. Cell 43, 192-202 (2011).
36. Durkin, S.G., Arlt, M.F., Howlett, N.G. & Glover, T.W. Depletion of CHK1, but not CHK2, induces chromosomal instability and breaks at common fragile sites. Oncogene 25, 4381-4388 (2006).
37. Ozeri-Galai, E., Schwartz, M., Rahat, A. & Kerem, B. Interplay between ATM and ATR in the regulation of common fragile site stability. Oncogene 27, 2109-2117 (2008).
38. Toledo, L.I. et al. ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 155, 1088-1103 (2013).
39. Brown, E.J. & Baltimore, D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397-402 (2000).
40. Brown, E.J. & Baltimore, D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev. 17, 615-628 (2003).
41. Forment, J.V., Blasius, M., Guerini, I. & Jackson, S.P. Structure-specific DNA endonuclease Mus81-Eme1 generates DNA damage caused by Chk1 inactivation. PLoS One 6, e23517 (2011).
42. Couch, F.B. et al. ATR phosphorylates SMARCAL1 to prevent replication fork collapse. Genes Dev. 27, 1610-1623 (2013).
43. Ragland, R.L. et al. RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells. Genes Dev. 27, 2259-2273 (2013).
44. Hodskinson, M.R. et al. Mouse SLX4 is a tumor suppressor that stimulates the activity of the nuclease XPF-ERCC1 in DNA cross-link repair. Mol. Cell 54, 472-484 (2014).
45. Svendsen, J.M. et al. Mammalian BTBD12 (SLX4) assembles a Holliday junction resolvase and is required for DNA repair. Cell 138, 63-77 (2009).
46. Takahashi, T., Nowakowski, R.S. & Caviness, V.S. Jr. The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J. Neurosci. 15, 6046-6057 (1995).
47. Snow, M.H.L. Gastrulation in the mouse: growth and regionalization of epiblast. J. Embryol. Exp. Morphol. 42, 293-303 (1977).
48. Murga, M. et al. A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging. Nat. Genet. 41, 891-898 (2009).
49. Despras, E., Daboussi, F., Hyrien, O., Marheineke, K. & Kannouche, P.L. ATR-Chk1 pathway is essential for resumption of DNA synthesis and cell survival in UV-irradiated XP variant cells. Hum. Mol. Genet. 19, 1690-1701 (2010).
50. Kawabata, T. et al. Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression. Mol. Cell 41, 543-553 (2011).
51. Kumagai, A., Lee, J., Yoo, H.Y. & Dunphy, W.G. TopBP1 activates the ATR-ATRIP complex. Cell 124, 943-955 (2006).
52. Bass, T.E. et al. ETAA1 acts at stalled replication forks to maintain genome integrity. Nat. Cell Biol. 18, 1185-1195 (2016).
53. Haahr, P. et al. Activation of the ATR kinase by the RPA-binding protein ETAA1. Nat. Cell Biol. 18, 1196-1207 (2016).
54. Duursma, A.M., Driscoll, R., Elias, J.E. & Cimprich, K.A. A role for the MRN complex in ATR activation via TOPBP1 recruitment. Mol. Cell 50, 116-122 (2013).
55. Higgs, M.R. et al. BOD1L is required to suppress deleterious resection of stressed replication forks. Mol. Cell 59, 462-477 (2015).
56. Singh, G. & Cooper, T.A. Minigene reporter for identification and analysis of cis elements and trans factors affecting pre-mRNA splicing. Biotechniques 41, 177-181 (2006).
57. Sirbu, B.M., Couch, F.B. & Cortez, D. Monitoring the spatiotemporal dynamics of proteins at replication forks and in assembled chromatin using isolation of proteins on nascent DNA. Nat. Protoc. 7, 594-605 (2012).
58. Conti, C. et al. Replication-fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells. Mol. Biol. Cell 18, 3059-3067 (2007).
59. Turriziani, B. et al. On-beads digestion in conjunction with data-dependent mass spectrometry: a shortcut to quantitative and dynamic interaction proteomics. Biology (Basel) 3, 320-332 (2014).